Is CHST6 p.Ala219Val (c.656C>T) pathogenic?

CHST6 p.Ala219Val (c.656C>T) is classified Conflicting classifications of pathogenicity in CHST6 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-12-22). AlphaMissense: likely benign (0.141); Ultra-rare (popmax 0.0121%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CHST6 p.Ala219Val (c.656C>T)?

CHST6 p.Ala219Val (c.656C>T) is associated with Inborn genetic diseases, macular corneal dystrophy (ClinVar).

How common is CHST6 p.Ala219Val (c.656C>T) in the general population?

CHST6 p.Ala219Val (c.656C>T) is ultra-rare (popmax 0.0121%, nfe) (gnomAD).

What do computational predictors say about CHST6 p.Ala219Val (c.656C>T)?

AlphaMissense predicts likely benign (score 0.141) — an in-silico prediction, not a clinical call.

CHST6 p.Ala219Val

c.656C>T · rs201743866 · VCV885986

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.141 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0121%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.141	likely benign
REVEL	0.207	benign-leaning
SaProt	LLR -12.15	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP -0.81, phastCons 0.98
Regional constraint	o/e 1.19	unconstrained · MANE · 1,184 bp · p 3.9e-06 · regional, not allelic
Overall
CADD	21.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0121% European (non-Finnish) · 143/1,179,034 alleles

Filtering AF 0.0105% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00982%

Overall 0.0209% 336/1,607,916 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.546%	183
Remaining individualsnot grpmax-eligible	0.0353%	2,834
European (non-Finnish)grpmax	0.0121%	8,245
Admixed American	0.00835%	11,980
African / African-American	0.00534%	18,726
Finnishnot grpmax-eligible	0.00168%	59,404

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CHST6
Protein: p.Ala219Val
Coding: c.656C>T
MANE Select: NM_021615
dbSNP: rs201743866
Type: single nucleotide variant
Location: chr16:75479173 (GRCh38)
Gene constraint: LOEUF 1.71 · pLI 0.26 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 90.66

Full CHST6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: macular corneal dystrophy

Similar variants

CHST6 p.Ala128Thr Likely pathogenic ★★ ⚠ same condition
CHST6 p.Arg127Cys Pathogenic ★★ same condition
CHST6 p.Arg140Ter Pathogenic ★★ same condition
CHST6 p.Arg211Gln Pathogenic ★★ ⚠ same condition
CHST6 p.Cys102Gly Pathogenic ★★ same condition
CHST6 p.Gln58Ter Pathogenic/Likely pathogenic ★★ same condition
CHST6 p.Glu274Lys Pathogenic ★★ same condition
CHST6 p.Leu200Arg Pathogenic ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/chst6-p-ala219val (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown